Help With Positive Blood Work & Negative Biopsy

[CeliacMommaX2]

Here are my son's labs:

 

IgA is 40 (15-160 is normal)

Endomysial antibody IgA (titer) 1:120

Endomysial antibody IgA is positive

Tissue Transglutam antibody is positive at 43 (less than 20 is negative)

 

Biopsy was negative.

 

When I called for the biopsy results, the GI clinic said he was negative for celiac and canceled our follow-up appointment.

 

Something doesn't seem right to me... why are his labs positive with a negative biopsy?  Is it because he's only 3?  What should I do now?

 

Thank you for anyone's help!!!

[ravenwoodglass]

What you should do now is get him on the diet. Positive blood work trumps negative biopsy especially on one so young. Do follow up with your ped for repeat blood testing after he has been gluten free for a while. Relief of symptoms combined with those positives going down is diagnostic. You ped should give you a celiac diagnosis based on that since you will need one for school. 

[Gemini]

This is the kind of medical "care" that makes me go crazy!!!!!!!

 

With a positive tTg and positive EMA, the odds are about 98-99% its Celiac.  I think the reason they don't say 100% with these results are because doctors cannot say absolute unless they see it on an x-ray.     And yes, I am being snarky here.  The reason his biopsy was negative was just what you said....he is 3 years old and hasn't developed enough damage to his small intestine for them to find with the biopsy method.  Your small intestine, if stretched out flat, has the surface area of a tennis court so you can see why a negative biopsy occurs often, even in the presence of full blown Celiac Disease.  There is no other disease that will give a positive on these blood tests, when done together.  EMA is very specific to Celiac.  I am amazed that your son popped positive on these 2 at such a young age but that is a VERY good thing because now you can change his diet to gluten free and he most likely will never go on to develop all the other autoimmune diseases we get when diagnosed at a much later age.    

 

Please find another doctor on this, not for diagnosis because he already has that.  You need someone who recognizes he has Celiac with these results because he does.  The other option is to keep him on a gluten filled diet and watch him get sicker and sicker, just to please the idiot doctor crowd. Many will only diagnose with a positive biopsy and that is malpractice, if you ask me. 

 

My niece has an almost 12 year old son who has Celiac, from all the conditions he has and his symptoms.  He was tested at a very young age and the testing was negative at 2 years old.  My family is in huge denial that there could be anyone else with it in the the family, except me.  You know what?  My great nephew is the size of an 8 year old and he has muscle weakness issues and asthma.  There could be other problems but they keep that hidden, their denial is so great.  I am afraid he will be really sick when he is older, with more and more autoimmune issues to come. Is that what you see your son's future as? 

 

Good luck to you and I hope you can find a doctor with more common sense than the ones you have right now.  Your son needs to be gluten free!  They can always re-test his blood work after following the diet for a while and see if they go back to normal.

[CeliacMommaX2]

This is the kind of medical "care" that makes me go crazy!!!!!!!

 

With a positive tTg and positive EMA, the odds are about 98-99% its Celiac.  I think the reason they don't say 100% with these results are because doctors cannot say absolute unless they see it on an x-ray.     And yes, I am being snarky here.  The reason his biopsy was negative was just what you said....he is 3 years old and hasn't developed enough damage to his small intestine for them to find with the biopsy method.  Your small intestine, if stretched out flat, has the surface area of a tennis court so you can see why a negative biopsy occurs often, even in the presence of full blown Celiac Disease.  There is no other disease that will give a positive on these blood tests, when done together.  EMA is very specific to Celiac.  I am amazed that your son popped positive on these 2 at such a young age but that is a VERY good thing because now you can change his diet to gluten free and he most likely will never go on to develop all the other autoimmune diseases we get when diagnosed at a much later age.    

 

Please find another doctor on this, not for diagnosis because he already has that.  You need someone who recognizes he has Celiac with these results because he does.  The other option is to keep him on a gluten filled diet and watch him get sicker and sicker, just to please the idiot doctor crowd. Many will only diagnose with a positive biopsy and that is malpractice, if you ask me. 

 

My niece has an almost 12 year old son who has Celiac, from all the conditions he has and his symptoms.  He was tested at a very young age and the testing was negative at 2 years old.  My family is in huge denial that there could be anyone else with it in the the family, except me.  You know what?  My great nephew is the size of an 8 year old and he has muscle weakness issues and asthma.  There could be other problems but they keep that hidden, their denial is so great.  I am afraid he will be really sick when he is older, with more and more autoimmune issues to come. Is that what you see your son's future as? 

 

Good luck to you and I hope you can find a doctor with more common sense than the ones you have right now.  Your son needs to be gluten free!  They can always re-test his blood work after following the diet for a while and see if they go back to normal.

Thank you so much for this validation.  That's been my understanding.  Do you have any scientific references you could pass along to validate that he very likely has celiac even with a negative biopsy?  I'm having trouble explaining this to people especially since the GI doctor said he doesn't have it!  Thank you!

[beth01]

I have to agree with Gemini, get a different doctor.  Ask for a referral to a pediatric gastro specialist that deals with Celiac.  If your doctor won't do that, find a ped who will diagnose with the blood tests results alone.  Any information you look up online about the EMA tests, it tells the specificity of the tests.  Print off information to take in and show to your doctor, ask him to explain this to you, why he thinks your child doesn't have Celiac.  It's bulls$#& doctors like this that leave people feeling like me for their whole lives. You don't need a diagnosis, but it sure will be easier with school if you have one.  Most schools aren't going to follow a 504 plan without a diagnosis, which comes in handy when you have a kid with Celiac in school. All sorts of school art supplies have gluten in them, and kids are always bringing treats to school.  I hope you have some luck finding a different doctor and getting some answers for your kid.

[Gemini]

The reason they are ignoring his blood work and saying he is negative for Celiac is because doctors who go by old standards will not diagnose Celiac unless they see flattened/blunted villi.  Your son will have to do more damage to his intestinal tract in order for them to have a better chance of hitting the sweet spot on biopsy.  That could take years and your son will be at high risk for complications and other AI diseases if you do so.  It would be easier to find another doctor who understands the disease progression better.  Ask for all copies of his testing, as is your right, and go to someone else. 

 

It just should not be this hard to diagnose the obvious and kids and adults should not have to choose between health and healing vs. pleasing a GI who waits until you get a lot sicker to give their Celiac Seal of Approval! 

[RMJ]

I would ask for a copy of the biopsy results with the pathology. Sometimes a Marsh 1 is called negative, but it might also be celiac in the early stages.

[BlessedMommy]

Perfectly said Gemini! I think that the whole thing makes about as much sense as telling a pre-diabetic that they need to keep eating sugar, because if they don't, the doctor won't be able to diagnose them with diabetes. Because after all, eating a low sugar diet is so extreme that you need a diagnosis in order to do it. LOL!

Especially in children--why take the risk of poor health, stunted growth, and additional AI diseases?

[greenbeanie]

Go to a new doctor, as others have said!

My daughter's tTG at age 4 was over 16x the upper limit of normal. They did not run the EMA, but both DGP tests were clear positives too. But her biospy "only" showed Marsh 2 damage. All of her doctors were surprised not to find more extensive damage on biopsy, given how high her blood tests were. Fortunately, we got a clear diagnosis even with only "mild villous blunting" in the duodenal bulb and high lymphocytes throughout. And the diagnosis was clearly correct. Why didn't they find more severe damage: Because she's a kid and heals fast? Because the tiny biopsies didn't hit the most damaged spot? Who knows...but thank goodness we had a GI who knew that Marsh 2 damage with three high positive blood tests and response to the diet was enough. I spent long enough trusting doctors who didn't know what they were doing. It took an outright comfrontation with two different PCPs to get someone to run the celiac panel in the first place - and awful as it was, it was clearly worth it. Don't worry if the GI thinks you're crazy, or is offended, or whatever...switch to a doctor who takes the problem seriously.

Good luck!

[nvsmom]

This report by the World Gastroenterolgy Organisation on Global Guidelines for Celiac Disease, shows the specificity of the tTG IgA and EMA IgA tests (see pages 10-12): Open Original Shared Link Specificity refers to what percentage of positive tests are caused by celiac disease. The EMA IgA has a specificity of 98-100%.  That is as specific as it can get!  Virtually everyone who gets a positive EMA IgA has celiac disease.  If you have a positive second test, then it is a sure thing.

 

I was diagnosed with a positive tTG IgA and EMA IgA.  My doctor didn't even bother with the biopsy because he was sure that celiac disease was the diagnosis.  I am sure your son has celiac disease.  

 

That EMA IgA titre is quite high too.  Since the EMA IgA shows more advanced disease, that means he was quite sick even if the damage wasn't biopsied.  The tTG IgA and EMA are very similar but the tTG IgA tends to show up first and attacks the intestines.  Then the EMA IgA will attempt to go into overkill and try to wipe off the top layer of the intestine (where the damage was) in an attempt to get rid of the problem.  It only happens in celiac disease.

 

Anyway, as I said, the titre is high.  I have only seen a few titres higher (1:320, and once in the last 3 years someone around here had a 1:640). For this test they keep doubling the dilution and give the result when the EMA IgA is no longer seen.  A positive is often 1:40 (I believe 1:20 is negative as is 1:10 and below), then comes 1:80 (positive), and then 1:160.... That's what my test was and I have been a celiac for many decades.  Don't doubt that test result.

 

Remember, the endoscopic biopsy has a sensitivity that can be as low as 80%, which means that it can miss up to 1 out of 5 celiacs - especially if fewer than 6 samples were taken.... It drives me batty that the endoscopy is still so highly regarded.  It is not 100% specific to celiac disease anyways.    (see Table 2 of this report for other positive biopsy causes Open Original Shared Link )

 

I went looking for more info on a negative biopsy.  You're right, it was a bit tough to find.  This is what I found:

Open Original Shared Link

 

This discusses a paper showing that biopsies are often not done in the prime celiac disease locations: Open Original Shared Link

or: Open Original Shared Link

 

Often a positive blood test with negative biopsy is called latent celiac disease, meaning it isn't in full force yet. (Which doesn't explain a positive EMA to me...)  If he keeps eating gluten it will eventually become active celiac disease, but I'm sure you don't want to wait that long.   Look up that one a bit.

 

If you want to chance another test you could always try the genetic DQ2 and DQ8 tests. Almost all celiacs have those genes so some doctors may look at it as a confirmation.  According to Fasano, a celiac disease expert, you just need four of the following to be considered a celiac:

 

 ...typical symptoms of celiac disease; positivity of serum celiac disease immunoglobulin, A class autoantibodies at high titer; human leukocyte antigen (HLA)-DQ2 or DQ8 genotypes; celiac enteropathy at the small bowel biopsy; and response to the gluten-free diet.

 

As shown here: Open Original Shared Link

 

Best wishes to you.  

[StephanieL]

BTDT-  Good luck with whatever you choose to do.  We did go gluten-free after the biopsy was negative with very high + blood work.  We have also had backlash from MAJOR Dr.'s in CeliacLand that said we need to challenge DS at 8 years old now because the biopsy was +.  I don't know what to tell you but you can try another Dr. but it's no guarantee they will help you.  All you need is one Dr. so you have something for school for accommodations your kid may need as they get older.

 

Hugs and good luck!!

[CeliacMommaX2]

This report by the World Gastroenterolgy Organisation on Global Guidelines for Celiac Disease, shows the specificity of the tTG IgA and EMA IgA tests (see pages 10-12): Open Original Shared Link Specificity refers to what percentage of positive tests are caused by celiac disease. The EMA IgA has a specificity of 98-100%.  That is as specific as it can get!  Virtually everyone who gets a positive EMA IgA has celiac disease.  If you have a positive second test, then it is a sure thing.

 

I was diagnosed with a positive tTG IgA and EMA IgA.  My doctor didn't even bother with the biopsy because he was sure that celiac disease was the diagnosis.  I am sure your son has celiac disease.  

 

That EMA IgA titre is quite high too.  Since the EMA IgA shows more advanced disease, that means he was quite sick even if the damage wasn't biopsied.  The tTG IgA and EMA are very similar but the tTG IgA tends to show up first and attacks the intestines.  Then the EMA IgA will attempt to go into overkill and try to wipe off the top layer of the intestine (where the damage was) in an attempt to get rid of the problem.  It only happens in celiac disease.

 

Anyway, as I said, the titre is high.  I have only seen a few titres higher (1:320, and once in the last 3 years someone around here had a 1:640). For this test they keep doubling the dilution and give the result when the EMA IgA is no longer seen.  A positive is often 1:40 (I believe 1:20 is negative as is 1:10 and below), then comes 1:80 (positive), and then 1:160.... That's what my test was and I have been a celiac for many decades.  Don't doubt that test result.

 

Remember, the endoscopic biopsy has a sensitivity that can be as low as 80%, which means that it can miss up to 1 out of 5 celiacs - especially if fewer than 6 samples were taken.... It drives me batty that the endoscopy is still so highly regarded.  It is not 100% specific to celiac disease anyways.    (see Table 2 of this report for other positive biopsy causes Open Original Shared Link )

 

I went looking for more info on a negative biopsy.  You're right, it was a bit tough to find.  This is what I found:

Open Original Shared Link

 

This discusses a paper showing that biopsies are often not done in the prime celiac disease locations: Open Original Shared Link

or: Open Original Shared Link

 

Often a positive blood test with negative biopsy is called latent celiac disease, meaning it isn't in full force yet. (Which doesn't explain a positive EMA to me...)  If he keeps eating gluten it will eventually become active celiac disease, but I'm sure you don't want to wait that long.   Look up that one a bit.

 

If you want to chance another test you could always try the genetic DQ2 and DQ8 tests. Almost all celiacs have those genes so some doctors may look at it as a confirmation.  According to Fasano, a celiac disease expert, you just need four of the following to be considered a celiac:

 

 ...typical symptoms of celiac disease; positivity of serum celiac disease immunoglobulin, A class autoantibodies at high titer; human leukocyte antigen (HLA)-DQ2 or DQ8 genotypes; celiac enteropathy at the small bowel biopsy; and response to the gluten-free diet.

 

As shown here: Open Original Shared Link

 

Best wishes to you.  

Thank you for your reply!  Great information.  My daughter was diagnosed a week before with a 1:320 and clearly visible damage with a positive biopsy.  We've turned our home gluten free, so my son will be gluten free anyway.  I hope we can talk to a doctor who will give us more answers and help. 

[nvsmom]

Good luck!  

[CeliacMommaX2]

I just recieved the report from the biopsy.  This is from the pathology report:

 

"Duodenum, biopsy:  Focal increased intraepithelial lymphocytes, otherwise unremarkable."

 

Does that mean anything?  Other than that everything was normal.

[murphy203]

I know the ped GIs are not overly plentiful, but you really need a new one!

[CeliacMommaX2]

I know the ped GIs are not overly plentiful, but you really need a new one!

We're debating going to the Celiac Center in Chicago.  Would they "consult" over the phone?  I'm not sure how this all works...

[nvsmom]

The World Gastroenterology report on celiac disease has this table in it:

 

Table 1

The modified Marsh classification of gluten-induced small-intestinal damage [33,34]

• Stage 0 Preinfiltrative mucosa; up to 30% of patients with dermatitis herpetiformis (DH) or gluten ataxia have small-intestinal biopsy specimens that appear normal

• Stage 1 Increase in the number of intraepithelial lymphocytes (IELs) to more than 30 per 100 enterocytes

• Stage 2 Crypt hyperplasia. In addition to the increased IELs, there is an increase in crypt depth without a reduction in villus height. Gluten challenge can induce these changes, which can also be seen in 20% of untreated patients with dermatitis herpetiformis and celiac disease

• Stage 3 Villous atrophy: A, partial; B, subtotal; C, total. This is the classic celiac lesion. It is found in 40% of DH patients. Despite marked mucosal changes, many individuals are asymptomatic and therefore classified as having subclinical or silent cases. This lesion is characteristic of, but not diagnostic of, celiac disease and can also be seen with severe giardiasis, infantile food sensitivities, graftversus-host disease, chronic ischemia of the small intestine, tropical sprue, immunoglobulin deficiencies, and other immune deficiencies and allograft rejection

Open Original Shared Link

 

It looks like he has Marsh 1 damage.  Doctors diagnose celiacs with Marsh 2 or higher.  Marsh 1 may be caused by something else, or it may be early celiac disease, sometimes called latent celiac disease.  If that is the case, it basically means there isn't enough damage YET to be officially diagnosed as a celiac but if gluten consumption continues, the patient may create enough damage for a diagnosis. 

 

Positive tests with a Marsh 1 is probably celiac.  The U of C even agrees that those with positive tests and a Marsh 1 will benefit from a gluten-free diet, even though they are (IMHO) too conservative to give a diagnosis of celiac disease in this case.  See the Making Sense of Marsh article: Open Original Shared Link

[StephanieL]

You may be able to have Chicago look at your slides. You would need to call them. They (most likely) will not consult over the phone. There are legal issues with insurance billing and having to actually see the patient. Though once you see them you should be able to do other stuff over the phone.  

[Fenrir]

Blood work tends to be extremely sensitive, so like others said a positive is 98-100% chance that you have celiac.

 

One thing I would like to mention is that it would be beneficial to see a GI specialist or another one. Also, may be worth getting the deaminated tests done.

 

For me, my TTG  was weak positive (which is still 98-100% chance) but my deaminated tests were very high and later on the biopsy put me at Marsh Grade 3b.

 

Any doc worth his/her salt will DX someone based on several signs symptoms and test results and not exclude a DX because of one unexpected test result. So, if he's having Celiac symptoms and a positive TTG that should be enough to know it's Celiac. The doctor should have suggested doing a 14 day gluten free trial and see how that goes. I have no doubt that the trial would have result in some relief of symptoms which would be another pointer that it is Celiac. 

[Fenrir]

Also, I don't know where you live but if the Twin Cities in MN is closer than Chicago, Minnesota Gastroenterology (MNGI) is a very good place to go as well. They DX'd me very fast and also have several Celiac patients that they monitor and they are very educated on Celiac as well. 

[murphy203]

CM, my experience with a consult at a specialty center (Hopkins neurology, in my case) is that you need to be referred by another specialist, and once you are there, they move VERY quickly and thoroughly as a team to get you answers. It will restore your faith in the medical community :-)

[StephanieL]

Any doc worth his/her salt will DX someone based on several signs symptoms and test results and not exclude a DX because of one unexpected test result. So, if he's having Celiac symptoms and a positive TTG that should be enough to know it's Celiac. 

 

I will warn that when dealing with kids, even the top Celiac Dr's see this differently.  I don't see the childs age posted but if they are younger then it's seen as a different ballgame in some regards.

[Fenrir]

I will warn that when dealing with kids, even the top Celiac Dr's see this differently.  I don't see the childs age posted but if they are younger then it's seen as a different ballgame in some regards.

No, is should not be any different for kids. One thing in a face of several others shouldn't exclude a DX. Has nothing do with being a kid or not.

[nvsmom]

No, is should not be any different for kids. One thing in a face of several others shouldn't exclude a DX. Has nothing do with being a kid or not.

...But doctors often do treat them differently.  It should all be the same, I agree, but it often isn't.

[StephanieL]

No, is should not be any different for kids. One thing in a face of several others shouldn't exclude a DX. Has nothing do with being a kid or not.

 

This isn't MY opinion.  This was from THE celiac guy in the US.  I'm not trying to debate anything just pointing out that they often do have different standards.